Cardiovascular system infections represent a serious problem in patients with congenital and rheumatic heart diseases, cardiac surgery, in drug addicts, and in patients with prosthetic heart valves, vascular grafts, or intravascular catheters. A common feature of these infections is underlying endothelial injury, and we plan to study the factors responsible for seeding microorganisms on endothelium or subendothelium of heart valves and vessel wall. The interaction of receptors on uninjured and injured endothelial cell layer with isotopically labeled microorganisms (staphylococci, streptococci, candida) that represent the most frequent offenders of cardiovascular system will be studied. The role of microbial receptors for fibrinogen and other plasma proteins in binding of microorganisms to elements of the vessel wall will be assessed. Changes in functional integrity of endothelial cells upon interaction with microbial agents will be determined by measurement of the vascular prostaglandin, prostacyclin (Prostaglandin I2). The possible role of blood platelets in anchoring bacteria to heart and blood vessel surfaces will be examined. A novel pharmacologic approach to this process will be assessed. The results of the proposed research will expand our knowledge of the mechanism of cardiovascular infections (endocarditis, infected vascular grafts, and prostheses) and will contribute to newer approaches to prevent their occurrence and the resulting malfunction of the heart and blood vessels.